WeChat***Medical Yao (ID: yiyao-jinduan006), author: Qing Li, title picture from: "Avatar: The Way of Water" When you stare at the abyss, the abyss is also staring at you.
A gene is a DN segment with genetic information, which stores all the information of the race, blood type, gestation, growth, apoptosis and other processes of life, and supports the basic structure and performance of life.
Since the day the gene was discovered, human beings have always wanted to conquer it, because by mastering the ability of gene editing, they have also mastered the infinite possibilities of life, such as genetic diseases that can be **many drugs cannot**. Since the birth of gene editing technology, there has been a constant controversy around its safety, ethics and other aspects.
Just last month, the balance of gene editing in commercialization was finally broken, when Vertex and CRISPR jointly announced that CRISPR Cas9 gene editing** (trade name: Casgevy) was approved for marketing in the UK for patients with transfusion-dependent thalassemia.
And last Friday, the FDA (Food and Drug Administration) announced the listing of Casgevy. On the same day, the gene editing **Lyfgenia, developed by Bluebird Bio, which has an indication that overlaps with Casgevy, was also approved.
When gene editing** begins to gradually obtain the largest market approval for innovative drugs, it means that by the end of 2023, mankind has opened the Pandora's box of "gene editing" in a real sense.
Angel's scalpel.
Gene editing technology is a technology that directionally modifies DNA gene sequences. Through this technology, humanity can theoretically take complete control of its own destiny.
The starting point of this technology is 1953, when Watson and Crick proposed the DNA double helix, which opened the prelude to modern molecular biology and introduced human cognition to the genetic level for the first time.
Although the structure of DNA was discovered very early, there was not much new progress in the concept of genes for a long timeIt wasn't until the 70s of the 20th century that humans discovered the possibility of gene editing. In the process of studying how bacteria defend against bacteriophages, scientists have discovered that there is a special enzyme in bacteria that is able to degrade the phage's DNA and thus protect the bacteria from phages, and this enzyme is the restriction enzyme.
Based on this discovery, humans began to experiment with the possibility of gene editing.
In 1996, the American gene company Sangamo Therapeutics launched the first generation of gene editing technology ZFNS, which can modify the genome of somatic cells and pluripotent stem cells, but it needs to design and synthesize complex protein modules, the construction cycle is long, the steps are cumbersome, and the binding of arbitrary target genes cannot be realized. Obviously, such a cumbersome step is difficult to monetize further.
Thirteen years after the advent of ZFNS, the second-generation gene editing technology TALENS was introduced. Although protein design is simplified compared to ZFNS, it still requires a significant amount of time to design and assemble. At the same time, it is more difficult to deliver to target cells due to the large volume, and high-throughput gene editing is not possible.
The complex mechanism greatly limits the further application of gene editing, which also points the way for the subsequent iterative path, that is, simplicity and efficiency.
Figure: Comparison of three generations of gene editing technology, **West China**.
In 2012, two young female scientists, Emmanuel Carpentier and Jennifer Doudner, developed the third generation of gene editing technology, CRISPR CAS. Compared with the previous two generations of technology, the biggest change in CRISPR Cas is the improvement of efficiency, the system is simple, accurate, high editing efficiency, and low operating cost, which greatly reduces the technical threshold and makes gene editing expected to realize the possibility of clinical application.
Carpentier and Doudna were awarded the Nobel Prize in Chemistry in 2020 based on the platform value of CRISPR Cas technology, and Carpentier later founded CRISPR Therapeutics and moved further towards clinical applications. The recently launched gene **Casgevy is the core product of CRISPR, and it has also become the world's first approved CRISPR gene editing**.
CASGEVY** is similar to CAR-T** in that cells are collected from the patient's body, then sent to the laboratory for modification, and then infused back into the patient's body to achieve a complete reversal of the disease. Casgevy modifies the patient's hematopoietic stem cells so that the cells produce high levels of fetal hemoglobin.
Figure: CAR-T and Genes, CICC.
There is no doubt that casgevy is only the beginning of human conquest of genes, and theoretically all types of diseases can be ** through gene editing, especially many genetic diseases with birth defects, which makes people see the hope of **. What's more, it has also been proposed to rejuvenate human beings by editing aging genes.
Humans who have mastered gene editing technology are like holding an "angel's scalpel" and have the ability to change their lives against the sky.
The devil's.
Breaking through the shackles of nature is not necessarily a good thing for human beings, and there are still too many unknowns to explore.
Gene editing is irreversible, and the edited genes will also be inherited after the edited cells are normal**. In other words, human changes to genes will always be passed on to future generations, and if the wrong genes are edited or the wrong genes are not currently visible, then genetic contamination will be caused.
Therefore, gene editing is not only an academic issue, but also a social and ethical issue.
In 2018, there was a "gene-edited baby" incident in my country. He Jiankui, an associate professor at Southern University of Science and Technology, announced that through gene editing, a pair of newborns have been successfully transformed, and they have a natural ability to resist the HIV virus at birth. However, this did not cause a sensation in the industry, but was jointly opposed by more than 100 scientists at home and abroad. In the end, He Jiankui was sentenced to 3 years in prison and fined 3 million yuan for "illegal medical practice".
Industrial technology is at the service of human beings. If safety and ethics cannot be addressed, the application of gene editing will be limited.
Putting these two issues aside, there are many practical issues that need to be faced at this stage if we want to comprehensively promote the commercialization of gene drugs. For example, at the application level, issues such as off-target effects, transcription efficiency, transportation issues, applicability, and long-term safety need to be solved urgently. In addition, the cost of gene editing** also limits its adoption, and the cost of casgevy** can be as high as $2 million.
Overall, the launch of Casgevy is only the first step in the commercialization of gene editing**. After all, CRISPR Cas technology has only been around for 11 years, and there is still a long way to go. In the face of new problems, we need to dare to face them head-on and overcome one problem after another, which is the driving force for human continuous progress.
Another arms race begins.
Gene editing technology has broad application prospects and huge market potential, attracting many high-quality domestic and foreign biotechnology companies to invest in research. Even in the cold winter of innovative drugs in 2022, there are still at least 7 companies in the field of gene ** that have obtained large financing of more than 100 million yuan against the trend, and Tessera Therapeutics has completed a super C round of more than 300 million US dollars.
In the face of such a hot investment in the primary market, countries around the world are constantly improving the ethical review system of science and technology to prevent the abuse of gene editing technology. For example, the "Opinions on Strengthening the Ethical Governance of Science and Technology" issued by China in 2022 is the first national-level document in China to put forward moral and ethical norms for gene editing.
What is certain is that the development and application of gene editing technology will bring the development of biological science into a new dimension, and the technology has broad application prospects in gene function research, drug development, and gene development, including cancer, Alzheimer's, cardiovascular diseases, etc.
But to make such a vision a realityAgain, it's about how humans use the tool, how they limit it, and not be driven by it.
Up to now, more than 50 companies in China have been involved in gene editing technology, mainly start-ups, and most of the pipeline research and development are in the early clinical stage, but these companies have not landed in the capital market for the time being.
Due to the late start of gene editing companies in China, the underlying intellectual property rights of CRISPR technology have been monopolized by Western countries, and they will still face the problem of "stuck neck" in technology research and development. At worst, you will pay high technology licensing fees, or you will be blocked by technology.
Given the power of gene editing technology, it is highly likely to be the next strategic technology. Therefore, whether we want to or not, objectively, another heavyweight arms race in the innovative drug track has begun.
WeChat***Medical Yao (ID: yiyao-jinduan006), Author: Qing Oak This content is the author's independent point of view and does not represent the position of Tiger Sniff. Do not do without permission**, please contact hezuo@huxiu for authorizationcom
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